Do PDE5 Inhibitors Improve Premature Ejaculation?
September 29, 2012
Premature ejaculation (PE) remains a highly prevalent and complex syndrome both to define and effectively treat in millions of men worldwide. While treatment is largely via pharmacotherapy with off-label indications, a recent systematic review sought to investigate the therapeutic role of PDE5 inhibitors.
Twenty-nine manuscripts that examined proposed mechanisms of action and 14 manuscripts that reported data from clinical trials were identified and reviewed. The review identified commonly reported supposed, central, and peripheral mechanisms of action of PDE5 inhibitors, predominantly centered on the role of nitrous oxide (NO) relative to second messenger pathways (e.g. CGMP) in the central nervous system and its relationship to smooth muscle in peripheral tissue.
Two different meta-analyses were performed including 1) PDE5 inhibitor monotherapy compared to placebo and 2) PDE5 inhibitor + SSRI versus placebo. The first meta-analysis found a significant effect of the PDE5 inhibitor treatment compared to placebo, while there was greater variability in the results in the group that received combination therapy. Overall, there was felt to be insufficient clinical evidence to support the use of PDE5 inhibitors in the treatment of PE.
Reference: Asimakopoulos AD, Miano R, Agro EF, et al. Does current scientific and clinical evidence support the use of phosphodiesterase type 5 inhibitors for the treatment of premature ejaculation? A systematic review and meta-analysis. J Sex Med 2012;9:2404-2416.
Potentially Permanent Sexual Side Effects of Finasteride
July 30, 2012
Finasteride has been implicated in the development of sexual side effects including decreased libido, decreased incidence and volume of orgasm, and erectile dysfunction. Previous trials have reported that while the incidence of these effects is generally low, they resolve over time and discontinuation of the medication. A cohort of 54 men who reported persistent sexual side effects associated with finasteride were reassessed 9-16 months after drug discontinuation. The Arizona Sexual Experience Scale (ASEX) was used to assess severity and incidence of symptoms, and 89% of male respondents met criteria for sexual dysfunction. The author reported that neither length of finasteride use nor duration of sexual side effects correlated to scores in sexual dysfunction. The blockage of conversion to dihydrotestosterone has been implicated in erectile dysfunction. Animal studies on dutasteride have shown increased collagen deposition and altered expression of neuronal and inducible nitric oxide synthase, whereas trials using finasteride have concluded a 26% weight reduction in the weight of the corpora cavernosa. To date, treatment with phosphodiesterase type-5 inhibitors and testosterone have not sufficiently restored sexual dysfunction in men treated with finasteride, as men who take finasteride do not typically have suppressed testosterone levels.
While selection bias in this trial may provide a significant limitation to its conclusions, the results may not apply to men with less severe side effects on the ASEX scale; men with more significant sexual side effects are more likely to participate in such a study. Additional research is needed to understand the potential underlying mechanisms of causation, as well as to understand strategies for treatment of these adverse effects.
Reference: Irwig MS. Persistent sexual side effects of finasteride: could they be permanent? J Sex Med 2012 (published online ahead of print)
What Affects The Degree of Penile Deformity In Peyronie Disease?
September 2, 2011
Peyronie disease (PD) is an acquired pathologic condition that results in inflammation and definitive fibrosis within the tunica albuginea, occurring in 4-7% of men. While the exact pathogenesis is not completely understood, the current theories posit that the condition results from repetitive microtrauma with subsequent scar formation. The aim of this study was to evaluate the relationship between the degree of penile curvature and clinical features of (PD) to determine predictive and causative factors.
Over 18 years, 1001 men with PD were evaluated retrospectively with regard to penile deformity, erectile function, and risk factors for cardiovascular disease.
The authors concluded that PD was predominantly determined in men during their fifth decade of life, proving that age is a positive correlating factor for development of ED. The most common comorbidities were diabetes mellitus (26%), hyperlipidemia (24%), hypertension (18%), and ischemic heart disease (8.5%). Systemic vascular risk factors were more commonly observed in patients with both PD and erectile dysfunction. Lateral side of deformity was also found to be a positive correlate as well. As a presenting symptom of PD, previous studies have reported ED in 4% to 80% of men. The authors admit that this study lacked definitive demographic data including controls of smoking, testosterone levels, obesity and marital status. Future research will investigate the relationship between these cofactors and PD severity.
Kadioglu A, Sanli O, Akman T, et al. Factors affecting the degree of penile deformity in Peyronie Disease: an analysis of 1001 patients. J Androl 2011;32:502-508.
The Controversial Role of PDE5 Inhibitors and Treatment of Premature Ejaculation
August 4, 2011
As treatments for erectile dysfunction were revolutionized in the late 1990's, therapies for premature ejaculation are still a novel area of sexual medicine that requires significant attention. Current research is exploring the role of pathogenesis of premature ejaculation to include genetic disruption and serotonergic pathways. The current therapeutic benefit of psychotherapy in premature ejaculation has been controversial.
A recent manuscript published in the Journal of Sexual Medicine comprised of expert opinions posits a new consensus on the recent literature. The controversial role of phosphodiesterase type 5 (PDE5) inhibitors in the treatment of premature ejaculation continues, as treatments for sexual dysfunction continue to be “mental and physical”, and the PDE5 inhibitors are rarely useful as primary therapy for premature ejaculation.
The authors conclude that PDE5 inhibitors are the first choice in the treatment of men with comorbid erectile dysfunction and premature ejaculation, yet rigorous evidence to support a potential concomitant relationship relative to nitrous oxide and other possible mechanisms are still limited.
Jannini EA, McMahon C, Chen J, et al. The controversial role of phosphodiesterase type 5 inhbitors in the treatment of premature ejaculation. J Sex Med 2011;8:2135-43.
Sexual behaviors, condom use and sexual health of Americans over 50
February 17, 2011
A recent study published in the Journal of Sexual Medicine, October 7, 2010 explored the frequency and types of sexual behavior, sexual pleasure and experience, and condom use in men and women age 50+. Traditionally, little has been known about the actual sexual behaviors of older adults. Why is this important? Because, nearly half of the people 65 and older in the United States are single.
The study collected a national sample of individuals from this target demographic within the past year. Participants were also asked about their experience during their most recent partnered sexual event. Bivariate or ordinal logistic regression models were used to investigate the relationship of age, health and partner status to sexual frequency and experience.
The authors found that 20-30% of men and women remained sexually active into their 80's. These sexually active men and women had a lower rate of single partner sexual encounters. The study found that for women, relationship status was a consistent predictor of a woman's satisfaction with the sexual encounter. For men, health status and performance was related to a man's positive evaluation of a sexual encounter. It was concluded that older adults who are sexually active well into their 80's have unique and diverse sexual health needs which healthcare providers need to be attentive to.